MS is a chronic neuroinflammatory disease with no cure. Most current MS therapies offer only palliative relief without repairing damaged nerve cells. Adult tissues such as bone marrow derived MSCs (BM-MSCs) may reduce neuroinflammation and promote nerve cell regeneration in MS, which are currently being tested in MS clinical trials. However, the application of adult-tissue derived MSCs has significant limitations since these cells must be obtained from a limited number of healthy donors, constraining the availability of this treatment and also resulting in variations in treatment quality.

Now researchers from ImStem, in collaboration with University of Connecticut Health Center (UCHC) and Advanced Cell Technology, Inc., demonstrates that hES-MSCs, which have unlimited stable supply, significantly reduce the disease severity in a mouse model of MS. They also found that hES-MSCs are more effective in treating animal model of MS than MSCs from bone marrow of adult human donors (BM-MSC). This work is published in the June 5th 2014 online edition of Stem Cell Reports, the official journal of International Society for Stem Cell Research (ISSCR) by Cell Press.

“The beauty of hES-MSCs (embryonic stem cell derived) is their consistently high efficacy in MS model. We found that BM-MSC (adult stem cell) lines show poor or no efficacy in MS animal model and also expressing more proinflammatory cytokines. This definitely adds more advantages to hES-MSCs, which are younger, purer and express the right factors" says the lead author Dr. Xiaofang Wang, CTO of ImStem.

"These great advantages perfectly match the requirements for safety and quality of clinical-grade MSCs as a potential therapy for autoimmune diseases.” says Dr. Ren-He Xu, corresponding author of the article, CSO of ImStem, now a professor at the University of Macau.

Dr. Joel Pachter, a UCHC collaborator, observed fluorescently labeled hES-MSCs but not BM-MSCs effectively penetrated the blood brain barrier and migrated into inflamed spinal cord. He remarks, "This difference is extraordinary as it could hold a key to the therapeutic action(s) of hES-MSCs. MSCs might require access to specific sites within the central nervous system in order to remediate disease."

"This was unexpected as bone marrow MSCs are widely believed to be effective in this EAE animal model. Our data indicate that the use of BM-MSCs is highly variable and there may be a previously unrecognized risk of poor outcome associated with proinflammatory cytokines produced by these cells," says Dr. Stephen Crocker, another UCHC collaborator.

“The cells not only reduced the clinical symptoms of multiple sclerosis but prevented demyelination, which disrupts the ability of the nervous system to communicate, resulting in a wide range of symptoms in patients, including blurred vision, loss of balance, slurred speech, tremors, numbness, extreme fatigue, paralysis and blindness,” says Dr. Robert Lanza, one of the senior authors from ACT.

Imstem was founded by Dr. Xiaofang Wang and Dr. Ren-He Xu, former director of UConn Stem Cell Core in 2012. In 2013, ImStem was awarded a $1.13M grant from the State of Connecticut Stem Cell Research Program and a $150,000 pre-seed fund from Connecticut Innovations. With these supports, ImStem has improved the hES-MSC technology with better efficiency and safety and has developed clinical grade hES-MSCs in its cGMP facility. ImStem is now seeking approval for Phase I clinical trials using its hES-MSCs and is looking for investors to expedite the progress.

"ImStem, our first spinoff company from the UConn Stem Cell Core, is uncovering the translational potential of hES-MSCs. ImStem’s cutting-edge work demonstrates the success of Connecticut’s Stem Cell and Regenerative Medicine funding program in moving stem cells from bench to bedside." says Dr. Marc Lalande, director of the University of Connecticut Stem Cell Institute.

“Connecticut’s investment in stem cells, especially human embryonic stem cells, continues to position our state as a leader in biomedical research,” said Governor Dannel P. Malloy. “This new study move us one step closer to a stem cell based clinical product which could improve people’s lives.”

About ImStem Biotechnology, Inc.
ImStem is a biotech company developing human embryonic stem cell based therapeutic products for tissue regeneration and autoimmune diseases. For more information, please visit: http://www.imstem.com.